The objective of this research proposal is to investigate the degree to which reticuloendothelial system (RES) depression during shock is due to hemolysis and erythrocyte phagocytosis. Additionally, the potential for increased circulating levels of the lysosomal enzyme, neuraminidase, to desialized erythrocytes and thereby increase the phagocytic load of erythrocytes during shock will be evaluated. The RES functions as an important host-defense mechanism during shock and the depression of this system may increase the susceptibility to shock and infection. Many studies have shown that RES blockade with foreign colloidal material results in increased susceptibility to shock and infection. It is proposed that the phagocytosis of altered native material (e.g., erythrocyte cellular debris, altered erythrocytes and products of activated coagulation) by the RES during sock results in a state of RES blockade. Shock patients, especially burn and trauma patients have a substantial degree of intravascular hemolysis, increased erythrocyte phagocytosis and activation of the coagulation system. The proposed experiments are designed to quantify the effect of the degree of hemolysis, erythrocyte phagocytosis, increased circulating neuraminidase activity and intravascular coagulation seen during experimental and clinical shock on RES phagocytic function and shock susceptibility. Hemolysis will be simulated by the injection of hemolyzed blood, erythrocyte phagocytosis will be induced by the injection of desialized or heat-damaged erythrocytes, circulating neuraminidase activity will be increased by the injection of purified neuraminidase and intravascular coagulation will be induced by the injection of thrombin. Additionally, the degree of hemolysis, as well as serum neuraminidase activity and erythrocyte sialic acid content will be determined in burn and trauma patients. This project, which brings together individuals from the Departments of Physiology and Surgery, will test a new concept concerning the mechanism of RES failure during shock.